Effect of drugs on human erythrocytes. I. Morphological changes and increase in fragility of erythrocytes treated with drugs.

To clarify the mechanism of hemolysis of human erythrocytes at higher drug concentrations, the effect of some drugs on osmotic and heat fragility, K+ efflux from the cells and morphological changes of the cells were studied. As a result of these studies, it was found that chlorpromazine and clemastine at 10-5M caused partial swelling, at 10-4M changes in cell shape to a sphere and at above 4×10-4M, at which the hemolysis is initiated, shrinkage and sinking of the cells. The mean cell volume of the cells increased by 4-5% at 5×10-5M and 8-9% at 10-4M. The cell volumes assumed at which concentration the hemolysis is initiated with drugs were 114-115% for these drugs. The initial swelling and subsequent shrinkage of the cells induced with drugs were found to be more predominant in concave portions of the cell membrane than in portions of the rim by scanning electron microscopic studies. The cell exposed to drugs at higher concentrations, at 5×10-5 and 10-4M, increased osmotic and heat fragility and the increased fragility was not reduced by washing and subsequent incubation in isotonic NaCl solution, in contrast with their stabilizing effect and their reversibility at the low concentrations. Efflux of K+ from the cells exposed to drugs was found to increase far more readily than that of hemoglobin.